The objective of this program is to establish a thematic multidisciplinary research center of excellence at the University of Louisville (UofL) named the Center for Cancer Immunology and Immunotherapy (CCII). The mission of the CCII is to conduct outstanding biomedical research that works towards harnessing the power of the immune system to eradicate cancer. There is currently a great deal of optimism about the prospects for cancer immunotherapies given the recent clinical successes of immune checkpoint inhibitors, oncolytic viruses, and adoptive cell transfer therapies. Immunotherapies have the potential to be used to treat all types of cancer and to induce long-lasting remissions or cures. However, more research and development is needed for cancer immunotherapy to reach its full potential. The University of Louisville is exceptionally qualified to be the home of the CCII for many reasons including our 10-year track record of conducting clinical trials of immunotherapeutic agents, unique resources that include access to human specimens from these trials, our senior investigators? expertise in cancer immunology, our focus on translational research, and the impact that this COBRE would have in a state with the highest cancer death rates in the nation. Importantly, the University of Louisville is highly invested in making this proposed center a success as best evidenced by more than $16.8M in institutional commitments over five years. The two PIs of the CCII program are highly regarded experts in the field who have made seminal contributions spanning from basic cancer immunology to pivotal clinical trials of cancer immunotherapies. Senior mentors with expertise in the thematic area and a strong history of funding, publications, mentoring, and study section service will support the CCII?s mentoring mission, as will a team of co-investigators with essential expertise (in administration, biostatistics, and bioinformatics) and Internal and External Advisory Committees. A Functional Immunomics Core will provide important new infrastructure and leverage existing resources (including other IDeA programs) to provide outstanding support to the four promising junior investigators who have been selected as the first cohort of CCII Project PIs. The four overall specific aims of the CCII are to: (1) Establish the administrative and mentoring infrastructure for the CCII; (2) Create a research core that provides new capabilities while leveraging existing facilities; (3) Support the research and career development of junior PIs in the thematic area; and (4) Develop and initiate a plan for long-term sustainability and growth of the CCII. We are confident that this new COBRE center will lead to the awarding of innovative R01 grants for 4-6 CCII junior investigators in the first five years and that many of these graduates will remain key members of this new COBRE to further build the center in the future. Most importantly, our combination of rigorous basic science with highly translational animal and human specimen studies should ultimately contribute to the development of new treatment strategies that will help to improve the outlook for the more than 17 million people worldwide who are diagnosed with cancer each year.